MCAT Organic Chemistry Review

Nitrogen- and Phosphorus-Containing Compounds

10.1 Amino Acids, Peptides, and Proteins

Amino acids are dipolar molecules that come together through a condensation reaction, forming peptides. Larger, folded peptide chains are considered proteins.

DESCRIPTION

Amino acids contain an amino group and a carboxyl group attached to a single carbon atom (the α-carbon). The other two substituents of the α-carbon are a hydrogen atom and a side chain referred to as the R group. This structure is shown in Figure 10.1.

Figure 10.1. Amino Acid Structure

The α-carbon, with its four different groups, is a chiral (stereogenic) center. Glycine, the simplest amino acid, is an exception to this rule because its R group is a hydrogen atom. Therefore, all amino acids—except for glycine—are optically active. The twenty naturally occurring amino acids in eukaryotes are all L-isomers. Therefore, by convention, the Fischer projection for an amino acid is drawn with the amino group on the left, as shown in Figure 10.2. L-amino acids have (S) configurations, except for cysteine, which is (R) because of the change in priority caused by the sulfur in its R group.

Figure 10.2. L- and D-Amino Acids

PROPERTIES

Amino acids, with their acidic carboxyl group and basic amino group, are amphoteric molecules. That is, they can act as both acids and bases. Amino groups can take on a positive charge by being protonated, and carboxyl groups can take on negative charges by being deprotonated. When an amino acid is put into solution, it will take on both of these charges, forming a dipolar ion or zwitterion, as shown in Figure 10.3. How an amino acid acts depends on the pH of the environment. In basic solutions, the amino acid can become fully deprotonated; in acidic solutions, it can become fully protonated.

Figure 10.3. Amino Acids Exist as Zwitterions (Dipolar Ions) at Neutral pH

BRIDGE

Amino acids are amphoteric molecules, just like water—they can act as both acids and bases. These acid–base characteristics (and titrations of amino acids) are discussed thoroughly in Chapter 1 of MCAT Biochemistry Review.

Aside from the zwitterionic properties common to every amino acid, each one has properties defined by its R group, or side chain. The 20 eukaryotic proteogenic amino acids are grouped into five categories: nonpolar nonaromatic, aromaticpolarnegatively charged (acidic), andpositively charged (basic). Nonpolar nonaromatic amino acids tend to have side chains that are saturated hydrocarbons, like alanine, valine, leucine, and isoleucine; they also include glycine, proline (which is cyclic, with a secondary amine), and methionine (which contains sulfur). Aromatic amino acids include tryptophan, phenylalanine, and tyrosine. Nonpolar amino acids—both nonaromatic and aromatic—are also hydrophobic and tend to be sequestered in the interior of proteins. Polar amino acids tend to have terminal groups containing oxygen, nitrogen, or sulfur. These include serine, threonine, asparagine, glutamine, and cysteine. Negatively charged (acidic) amino acids include aspartic acid and glutamic acid. These amino acids have terminal carboxylate anions in their R groups. Finally, positively charged (basic) amino acids, including arginine, lysine, and histidine, have a protonated amino group in their R groups. Polar, acidic, and basic amino acids are all hydrophilic and tend to form hydrogen bonds with water in aqueous solution.

Amino acids undergo condensation reactions to form peptide bonds. The molecules these bonds form, called polypeptides, are the base unit of proteins. The reverse reaction, hydrolysis of the peptide bond, is catalyzed by a strong acid or base. Both of these reactions are shown in Figure 10.4.

Figure 10.4. Peptide Bond Formation and Cleavage

Like other carbonyl-containing functional groups, amides have two resonance structures, as shown in Figure 10.5. The true structure of the amide bond is therefore a hybrid of these two structures, with partial double-bond character between the nitrogen atom and the carbonyl carbon. This double-bond character limits rotation about the C–N bond, which adds to the rigidity and stability of the backbone of proteins. The single bonds on either side of the peptide bond, on the other hand, permit free rotation.

Figure 10.5. Resonance in the Peptide Bond

KEY CONCEPT

Rotation is limited around the peptide bond because resonance gives the C–N bond partial double-bond character.

MCAT Concept Check 10.1:

Before you move on, assess your understanding of the material with these questions.

1.    What makes glycine unique among the amino acids?

2.    Amino acids are amphoteric. What does this mean? What functional groups give amino acids this characteristic?

3.    How are peptide bonds formed and cleaved?

4.    Why is the C–N bond of an amide planar?